Acidic solid oral compositions without erosive potential in saliva and method for determining erosive potential in saliva

ABSTRACT

Acidic oral compositions having calcium contents and effective pH-values in the area indicated by grey-tone in FIG.  2  are non-erosive in saliva and capable of stimulating saliva production, even in “dry mouth” patients. A new multi-step test method for determining erosive potential in saliva has been used for identifying the compositions.

BACKGROUND

Technical Field

The present invention relates in general to solid oral compositions,which provide an acidic reaction when dissolved in an aqueous liquidlike saliva. More particularly, the present invention relates to acidicsolid oral compositions with reduced erosive potential in saliva and tothe use of a calcium component and an acid component in particularamounts for reduction of the erosive potential. The invention alsorelates to a method for stimulating saliva production, and to the use ofa calcium component and an acid component for the manufacture of anacidic solid oral composition for alleviating the sufferings of anindividual having impaired saliva production. Furthermore the inventionrelates to a method for determining the erosive potential of an oralcomposition in saliva.

Description of the Related Art

Dental erosion is the loss of dental hard tissue by a chemical processthat does not involve bacteria and is therefore not associated withdental plaque. One of the most important factors with respect to dentalerosion is extrinsic exposure to acid. Dental erosion has been shown tobe an increasing threat to dental health, and frequent soft drinkconsumption as well as consumption of acid-containing foodstuffs (citrusfruits and sweets) are important factors in the development of dentalerosion. The general awareness of dental erosion is increasing rapidly.It is therefore important for manufacturers to think of new ways todevelop foodstuffs that satisfy consumers' need of acidic stimuli andthat at the same time do not cause or reduces dental erosion.

Generally, low pH in the oral cavity and around the teeth is the majorcause of dental erosion. The hard part of human teeth is composed ofhydroxyapatite crystals (HAp) (Ca₁₀(PO₄)₆(OH)₂). In the teeth the HApcrystals are arranged in a condensed structure making up the hardesttissue in the body. However, if the teeth are exposed to fluids with alow pH (like acidic soft drinks or saliva containing dissolved acidiccandy) the HAp crystals will dissolve and dental erosion will developdue to shortness of Ca²⁺, PO₄ ³⁻ and OH⁻ ions in the fluid (componentsof HAp).

Beverages supplemented with significant levels of calcium fornutritional purposes have been suggested in the prior art. Dietarycalcium inadequacy may be a contributing cause to osteoporosis, at leastwithin some populations. For example, a positive correlation betweencalcium intake and bone mass has been found across many age groups. Ithas also been suggested that the level of calcium intake earlier in lifedirectly influences the peak bone mass achieved at skeletal maturity.

U.S. Pat. No. 5,028,446 discloses a process for preparing rapidlysolubilized calcium fumarate for use in the production of calciumfortified beverages. The process involves the preparation of a mixtureof fumaric acid and a calcium-containing base, wherein the mole ratio ofthe calcium to the fumarate is ranging from 1:2 to about 1:1. Themixture of fumaric acid and calcium is indicated to possess an improvedsolubility characteristic usable in the production of calcium fortifiedbeverages, such as tea.

Another calcium-fortified beverage is disclosed in EP 227 174. Thebeverage is substantially free of sugar alcohol and comprises a certainweight ratio of calcium to a mixture of citric, malic, and phosphoricacid of 1/4 to 1/7. The beverage is said to have a satisfactory initialtaste and mouth feel, substantial freedom from objectionable aftertasteand desirable calcium absorbability/bioavailability properties.Typically, the pH of the produced beverages is around 4.3.

A dry mixture intended for reconstitution comprising citric acid and oneor more calcium compounds is disclosed in WO 88/03762. The instantbeverage may comprise a mole ratio of calcium/citric acid between 0.6and about 3.0. The solubility of the mixtures having varying ratiosbetween calcium and citric acid depended on the pH. The solubility wastested for pH values between 2.0 and 7.0, an actual drink as preparedhaving a pH of 4.15 and above. The composition has a utility as a liquiddietary calcium supplement.

U.S. Pat. No. 3,734,742 discloses a sealed or canned bottled aqueousbeverage containing at least about 80% of water and having a pH of from2.0 to 3.4, an ascorbic acid content of from 0.056 to 1.120 mg/ml and aferrous ion content of from 0.008 to 0.15 mg/ml. The object of this USpatent is to obtain a beverage supplemented with iron and ascorbic acid.

None of the above mentioned references relate to dental erosion.

As mentioned in the introduction, acidic compositions for consumptiontend to erode tooth components, notably the content of hydroxyapatite.Several publications address this issue. EP 634 110 A2 pertains to anutrient, vitamin and mineral fortified, fruit based liquid foodstuffhaving an acid content of at least 5 g/l as tartaric acid and a contentof calcium phosphate of at least 2 g/l. The pH is below 4.5, with actualvalues between 3.9 and 4.15. The calcium phosphate is said to reduce thenegative influence of the acidic liquid foodstuff on the toothsubstance. Another liquid oral composition comprising a calcium compoundand an acid compound is disclosed in WO 97/30601. The liquid compositioncontains calcium in the range of 0.3 to 0.8 moles per mole of acid andas an important feature the amount of calcium and acid in thecomposition is selected so that the pH of the composition is from 3.5 to4.5. A further acidic beverage, which is said to inhibit the erosion oftooth enamel, is disclosed in U.S. Pat. No. 5,108,761. The beverageaccording to U.S. Pat. No. 5,108,761 includes calcium citrate malate forreduction of dental erosion.

An acidic medical preparation has been disclosed in U.S. Pat. No.4,080,440 disclosing a process for remineralising dental enamel. Theprocess implies applying a freshly prepared metastable aqueous solutionto the tooth surface. The solution has a pH of about 2.5 to about 4.0and comprises a soluble calcium salt and a soluble phosphate salt insuch amounts that the molar ratio of calcium ions to phosphate ions isin the very broad range from 0.01 to 100. The preparation is notintended for being consumed.

Also edible or chewable solid or semi-solid compositions, which show areduced tendency to erosion of teeth have been disclosed in the priorart. WO 98/13013 discloses e.g. a chewing gum or a candy capable ofremineralising tooth lesions. The composition in question comprises acationic component comprising at least one partially water-solublecalcium salt, an anionic component comprising at least one water-solublephosphate salt and a separating component. The pH of the compositionwhen dissolved in water or saliva is from greater than about 4.0 toabout 10.0. Because of the partial water-solubility of the calcium salt,the calcium cations and the phosphate anions in the mixed aqueouscomposition remains soluble for a period of time sufficient to allow thecations and anions to diffuse through the surface of the tooth to thesubsurface or dentine, where the diffused cations and anions react toform an insoluble precipitate on the lesion for remineralisationthereof.

WO 99/08550, having the same inventor as WO 97/30601, discloses an acidcontaining solid or semi-solid composition with reduced tooth erosion.The composition contains calcium in the range of 0.3 to 0.8 moles permole of acid and the proportion of calcium and acid in the compositionis selected so that the effective pH of the composition, when dissolvedin a liquid such as water, is from 3.5 to 4.5. While a tooth protectionmay be obtained by using this composition, the saliva stimulating effectwill be limited due to the comparatively high pH value, and the tasteexperience thereby impaired. This is particularly critical in relationto such products as boiled sweets, candies, lollipops, jellies, chewinggums, drops, pastilles, lozenges, tablets, ice cream and sorbets.

In U.S. Pat. No. 2004/0091517 A1 having the inventor of WO97/30601 andWO99/08550 as co-inventor, acidic oral compositions having effective pHvalues down to 2.2, especially acid beverages with a pH between 2.2 and5.5, are disclosed. The invention according to said application residesin the use of a polyphosphate being a phosphate polymer wherein thenumber of phosphate groups (n) is at least 3, as a tooth erosioninhibitor. The polyphosphate may be used in conjunction with calciumbeing present in amounts up to 0.8 moles per mole of acidulant. Howeverpolyphosphates are undesirable from different points of view,particularly in the preparation of hard-boiled candy and other products,which are subjected to heating. By heating of the acidic compositionthere is a risk of the polyphosphate becoming converted to otherphosphates, which are known to have an unpleasant taste. Furthermore, byhaving both calcium and phosphate in high concentrations, there is arisk of the calcium precipitating out as non-useful calcium phosphatecompounds.

The present inventors suggest decreasing the pH in order to obtain abetter taste experience and a pronounced saliva stimulating effect. Thishas been possible while maintaining a composition, which is non-erosivein saliva—without the use of a polyphosphate as disclosed in US2004/0091517 A1.

The increased saliva production results in an increased protectiveeffect from the constituents of the saliva itself. As a furtherinteresting point, the non-erosive effect of the composition seems to beobtainable even in so-called “dry-mouth” individuals suffering fromimpaired saliva secretion.

This surprising finding is the result of extensive research carried outby the present inventors, which among others has resulted in a new testmethod for erosive potential, which in a simple and reliable mannertakes into account the complex conditions in saliva in the human mouthin the presence of the acidic oral composition, such as a candy. Thistest method represents a particular aspect of the present invention.

When solid and semisolid compositions are sucked, saliva becomes thematrix for the compositions, and thereby saliva influences all effectsthat the compositions may have on teeth. The method according to theinvention provides, in contrast to theoretical calculations based onphysical chemistry, the unique feature of accounting for all protectivefactors present in human saliva, organic as well as inorganic. Thesefactors include the salivary proteins (around 2 mg/ml), the salivabuffer capacity, the saliva calcium and phosphate, saliva fluoride, andtrace amounts of other ions present in saliva. The salivary proteinshave the ability to form a protective coating, also known as theacquired pellicle, on the surface of teeth. Due to this ability, thesalivary proteins will protect teeth and tooth substance against acidinduced erosion. However, the effect of this protein coating on tootherosion in different individuals cannot be quantified by any knownmethods of calculation, it has to be subjected to testing. The salivabuffer capacity, which originates from salivary bicarbonate, phosphate,and proteins, will also protect teeth and tooth substance against acidinduced erosion, and this effect also has to be accounted for by thetest method. Thus, when an acidic oral composition is dissolved insaliva, the pH will drop, however, the pH drop will be counteracted bythe three salivary buffer systems resulting in an increased salivary pHand thereby reduced erosive effect. Saliva also contains some calciumand phosphate, which will help to increase the degree of saturation withrespect to hydroxyapatite and thereby decrease acid induced erosiveeffects. In this context, saliva also contains fluoride, mainlyoriginating from foodstuffs and toothpaste, and this fluoride willincrease the effective degree of saturation with respect to toothsubstance, and thereby also decrease acid induced erosive effects.Finally, trace amounts of other ions originating from foodstuffs anddrinking water may also have an effect on tooth substance dissolution.In concert, the three last factors may have considerable protectiveeffects that cannot be directly predicted by calculation and thereforealso needs to be tested by the method provided. The method according tothe invention provides an efficient means for determining thedemineralization of hydroxyapatite and thereby evaluation the erosivepotential of any solid and semisolid composition dissolved in saliva.

BRIEF SUMMARY

The invention provides an acidic solid oral composition with reducederosive potential in saliva, comprising a calcium component and an acidcomponent, wherein the amounts of calcium component and acid componentin the solid oral composition are adjusted so as to provide

-   -   (i) a pH in the range of 2.2 to 3.2, when the solid oral        composition is dissolved in an equal amount by weight of highly        purified water, and    -   (ii) a calcium content in the acidic solid oral composition        within the following limits:

175-50·pH calcium content (mmol/kg)≦660-200·pH,

the pH being determined as indicated above,

with the proviso that the composition does not include a polyphosphatebeing a phosphate polymer wherein the number of phosphate groups (n) isat least 3.

It was surprisingly found that a reduced erosive potential wasobtainable by a composition having a pH between 2.2 to 3.2, without theuse of any polyphosphate as in US/2004/0091517 A1.

It was to be expected that the relatively long contact time between theoral solid compositions of the invention and the teeth would damage thetooth hydroxyapatite. Herein, it is reported that certain amounts ofcalcium component reduces the erosive potential in saliva for acomposition of comparatively low pH value, even in situations where theamount of calcium results in the saliva being under-saturated withrespect to calcium.

A beverage normally only has a contact time with teeth of around a fewseconds before it is swallowed, whereas an oral composition intended forsucking or chewing remains in the oral cavity for several minutes. Theacidic solid oral composition according to the invention allows for asubstantial saliva stimulation, a better taste and at the same time, asubstantively reduced erosive potential. The taste can be furtherimproved by addition of one or more sweetening and/or flavouring agents.Such additives are also known to stimulate the saliva production.

In an aspect of the invention the saliva stimulating property of thepresent oral composition is used for alleviating the sufferings ofindividuals having impaired saliva production. Impaired salivaproduction can e.g. be observed in diseases such as Sjögren's syndrome,cystic fibrosis, diabetes or eating disorders, or by therapeutictreatments, such as medical treatments or radiotherapy.

Dry mouth patients commonly use acidic candies for reduction of theirdiscomfort, but a serious drawback of the consumption of large amountsof candies is that the teeth of dry mouth patients are at a higher riskof erosion.

When healthy individuals are enjoying acidic solid oral compositions,like candies, the buffer capacity of the saliva counteracts the low pHinduced by the dissolution of an oral composition. However, for patientssuffering from impaired saliva production the ability to counteract thesevere effect of the low pH is reduced due to low concentrations ofbuffers in saliva of dry mouth patients.

Therefore, there is a need for acidic oral compositions having a highability to stimulate saliva production and being without erosivepotential. The present invention suggests a solution to this need.

As used herein, the term “solid oral composition” refers to a producthaving a hard consistency or a gum-like consistency and which can beeaten, sucked or chewed in the oral cavity. The term solid refers to thestate at the temperature of use. The present invention particularlyconcerns solid or semi-solid substances for oral processing such asboiled sweets, candies, tablets, lozenges, lollipops, jellies, chewinggums, drops, and the like. In an aspect of the invention, semi-solidcompositions also include products such as ice cream and sorbets.

The solid oral composition according to the invention may be partiallyor fully soluble in water. Sweets like jellies and candies are usuallyfully soluble in water, whereas chewing gums usually only partiallydissolves in water. When the pH of the solid oral composition ismeasured an amount of the composition is mixed with an equal amount byweight of highly purified water (Ph. Eur.). If necessary, the oralcomposition can be physically worked to obtain an aqueous phase, inwhich soluble components from the oral composition is dissolved.Remaining parts of the solid composition may be left in a solid phasedue to saturation of the aqueous phase or insolubility of somecomponents of the composition. A pH measured in this manner is referredto herein as “effective pH”.

The actual amount of calcium component and acid component depends on theformulation of the solid oral composition of the invention. E.g. calciumlactate pentahydrate could be included in 1 kg mass for making candy, inan amount of 10 to 35 grams, corresponding to a calcium concentration of33 to 114 mmol/kg (33 to 114 mM). The amount of acidic component isselected so as to obtain an effective pH within the range 2.2 to 3.2.The specific amount of acidic component depends on the type of acidiccomponent, the buffer capacity of the oral composition etc. E.g., theconcentration of acid component could be in the range of 33 to 132 mM(33 to 132 mmol/kg), corresponding to 5 to 20 g of tartaric acid per kg.

The calcium component is in general non-toxic and acceptable as a foodsupplement. Furthermore, the calcium component is in general capable ofbeing sufficiently dissolved in the oral cavity to allow for aliberation of free calcium ions. Suitably, the calcium component isselected among calcium carbonate, calcium hydroxide, calcium citrate,calcium malate, calcium lactate, calcium chloride, calciumglycerophosphate, calcium acetate, calcium sulphate, and calciumformate, or hydrates thereof. The calcium component may also be acombination of two or more of the compounds listed above. Preferably,the calcium component is calcium lactate.

The acid component of the invention is suitably selected from the groupof edible acids naturally produced in plants or animals. However,artificial acids may also be used. Preferably, the acid component isselected from the group consisting of citric acid, malic acid, ascorbicacid, tartaric acid, acetic acid, fumaric acid and lactic acid. The acidcomponent can be added during the manufacture of the oral composition orcan be present in a fruit concentrate or similar, used as base for themanufacture of the oral composition.

The amount of acid used in the manufacture of the solid oral compositionof the invention, is suitably selected so as to provide a certainpredetermined pH, when the oral composition is dissolved in an equalamount by weight of highly purified water, e.g. Millipore® water.Millipore® water is demineralised, distilled, filtrated andion-exchanged water, which has furthermore been subjected to reverseosmosis. For the purpose of this pH measurement it is of importance thatthe water does not contain buffer salts. According to the invention theacid is adjusted in the oral composition in such manner that theeffective pH is between 2.2 and 3.2. In a preferred aspect, theeffective pH is between 2.5 and 3.2, particularly between 2.6 and 3.1.

Acidic solid oral compositions according to the invention have moleratios of calcium component to acid component within the range from 0.1to 1.40 and preferably between 0.3 and 0.8. More preferred the moleratio of calcium component to acid component is between 0.4 and 0.7.

The composition of the invention may be composed of just the calcium andthe acid component. Suitably, however, the calcium and the acidcomponent are comprised in a carrier. The carrier may e.g. form avitreous, crystalline, or gum-like basic structure. The choice ofcarrier depends on the product intended. F. inst. a carrier forming avitreous or crystalline structure may be selected, when a candy isproduced and a carrier forming a gum-like structure may be selected,when the product is a chewing gum or a jelly.

Typically, a sugar and/or a sugar substitute is selected as the carrierwhen a candy is produced. Suitable sugars include sucrose, isomalt,maltose, glucose, fructose, invert sugar, syrup, etc. The sugarsubstitute, or sweetener, may e.g. be selected among saccharin,dextrose, levulose, sodium cyclamate, Acesulfame-K and aspartame. Thesugar component may be a mixture of a sugar and a sweetener. The sugarcomponent may also be a combination of different sugars. In accordancewith one aspect of the invention a candy is produced by dissolution of asugar component in water followed by cooking of the solution until somuch water has evaporated that a temperature of 105 to 160° C. isobtained. The mixture is now viscous and referred to as a dough. Theacid component and the calcium component are added to the dough followedby mixing. Usually, the dough is also mixed with a flavouring agent anda colour. The dough is then cut into appropriate pieces and allowed tocool.

A jelly is usually based on gelatine. However, other polymers having anatural origin or synthetic polymers may also be used. Initially, thegelatine is dissolved in water followed by addition of sugar components,e.g. sucrose or glucose syrup or any of the other sugar componentsmentioned above. The homogenous mixture is then boiled until a certaindry matter content is obtained, due to evaporation of water. Then theremaining components are added to the mixture, including the calcium andthe acid component. Flavour and colour is normally added at this stage.After thorough mixing the blend is cast or extruded to suitable forms.

As mentioned above, the erosive potential of a composition in a complexfluid like saliva cannot be theoretically calculated, but will have tobe tested.

For testing of the erosive potential a new test method has beendeveloped, which in a simple and reliable manner takes into account theeffect of the oral composition on the production and composition of thesaliva under in vivo conditions. This new test method represents aparticular aspect of the present invention.

Accordingly the present invention provides a method for determining theerosive potential in saliva of an oral composition, comprising the stepsof:

-   -   a) bringing the oral composition to be tested into contact with        saliva in the mouth,    -   b) collecting a sample of the saliva under conditions so as to        prevent CO₂ from escaping from the sample,    -   c) measuring the pH of the sample collected under b),    -   d) removing CO₂ from the sample, optionally assisted by vacuum        and/or addition of a non-volatile acid,    -   e) adjusting the pH of the sample to the value measured under c)        using a non-volatile acid or, if necessary, a non-volatile base,    -   f) adding tooth substance to the sample obtained from step e),        and observing any rise in the pH,    -   g) if a rise in pH is observed in step f), titrating the sample        to the pH value measured in c) using an acid, and    -   h) calculating the amount of tooth substance eroded based on the        amount of acid consumed in step g).

The initial measurement of the pH in step c) may be performed in anysuitable way. As an example, a pH electrode may be present in the mouthcavity to record the pH at the time the sample is taken. However, toincrease the user convenience the saliva sample is typically collectedin a closed system preventing CO₂ from escaping from the sample. Asuitable way of collecting the sample is to use a syringe for withdrawalfrom the mouth cavity of a suitable amount of saliva. A sample of salivafrom the mouth cavity of the test person is usually taken prior toadministering the oral composition. Then the oral composition to betested is brought into contact with saliva in the mouth for an adequateperiod. In case of a solid oral composition, the oral composition issucked or chewed habitually for an adequate period of time before asaliva sample is withdrawn. A single or multiple samples may becollected. Multiple samples could e.g. be collected by collecting asample every 30 seconds or every minute for a total of five minutes. Inthe event only a single sample is collected it may suitably be withdrawnafter it has been secured that sufficient oral composition has dissolvedin the saliva of the mouth, e.g. after 3 minutes. During the entire testperiod the test person is requested not to swallow the oral compositionor any saliva.

After measuring the pH, the CO₂ is removed from the sample. Variousmethods for removing CO₂ are available for the skilled person, includingsonification, vacuum treatment, and stripping. Generally, vacuum is usedtogether with stirring. The CO₂ removal may be assisted by addition of anon-volatile acid. The non-volatile acid is usually a strong acid. Thestrong acid can be selected from the group consisting of aqueoussolutions of HCl or HNO₃. When the CO₂ has been removed, the pH of thesample is adjusted to the pH originally measured using a non-volatileacid or, if necessary, a non-volatile base. The latter may e.g. berelevant, if the amount of non-volatile acid added for assisting theremoval of CO₂ has brought the pH of the sample below the pH valuemeasured under c).

The saliva sample has now been depleted of its content of CO₂ butretained its original acidity. Next, a tooth substance is added to testwhether any erosion occurs. The tooth substance can originate fromhumans or animals or can be artificial. If the tooth material originatesfrom humans or animals, it is usually ground to obtain a high surfacearea. It is, however, preferred to use artificial tooth substances, i.e.substances of non-dental origin, in order to avoid the variationappearing between individuals. The primary component of enamel anddentin in teeth is hydroxyapatite. Thus, in a preferred embodiment,hydroxyapatite is selected as the tooth substance, particularlyhydroxyapatite (Ca₁₀(PO₄)₆(OH)₂) with a solubility product ofapproximately 117.3 (pK) at SATP (Standard Ambient Temperature andPressure).

The tooth substance can be left in the saliva for a certain period oftime before the titration is performed. Due to the thermodynamic natureof the solubility product of hydroxyapatite, the sample should be keptat a temperature, not higher than body temperature and not lower than20° C., until the titration is performed.

The amount of acid used for the titration is equivalent to the amount ofdissolved tooth substance. Thus, 1 mM hydroxyapatite (M_(W) 1005)requires 14 mM H⁺ (M_(W) 1) due to the reaction:Ca₁₀(PO₄)₆(OH)₂→10Ca²⁺+6PO₄ ³⁻+2OH⁻→10Ca²⁺+6H₂PO₄ ⁻+2H₂O, provided thatthe pH in the saliva is in the range from 3 to 5. Therefore the use of14 μl 1N acid, such as 1M HCl (i.e. 14 μg H⁺) for back titrationreflects the dissolution of 1005 μg hydroxyapatite, and the use of 1 μl1M HCl reflects the dissolution of 72 μg HAp (i.e. 1005/14).

Accordingly, the amount of hydroxyapatite crystals lost per minute inthe candy containing saliva could be back calculated from the number ofμl 1M HCl needed to reach the pH obtained in step c) by the followingequation:

μg HAp lost=(μl acid used×72)/minutes of dissolution

In the event the solid oral composition does not provoke any rise in thepH in step f) the method is not continued to steps g) and h) and it isconcluded that the tested oral composition is non-erosive. If however, apH rise in step f) is observed, steps g) and h) provide a quantificationof the amount of lost (or eroded) hydroxyapatite.

The method provides the unique feature of accounting for the influenceof the complex conditions in saliva in the human mouth on dentalerosion. Furthermore, the variable contribution of CO₂ in the samples tothe pH over time is avoided. As the pH is the most important singlefactor in relation to erosion of teeth, the present method provides anefficient means for predicting the demineralisation of hydroxyapatiteand thereby evaluating the erosive potential in saliva.

Acidic solid oral compositions according to the invention, which, whentested by the method according to the invention in randomly selectedhealthy test persons, do not result in any rise in pH in step f) withina period of 5 minutes for at least 90% of the test persons, represent apreferred aspect.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 illustrates the amount of tooth substance lost by dental erosionversus time by testing of a candy according to the invention and acontrol candy, respectively.

FIG. 2 is a graphic representation illustrating calcium content inmmol/kg versus effective pH for compositions according to the inventionas well as some compositions, which are not according to the invention.

As will appear from the explanations given above, the erosive potentialof a composition in saliva cannot be theoretically calculated, but willhave to be tested. However based on experiments with compositions, whichhave been shown to be non-erosive, the following correlation between theamount of calcium component and the effective pH was initially found:

calcium content (mM)=650±10-200·pH

The actual pH-ranges, within which the correlation applied were notestablished initially, but at least the correlation was expected toexist within the pH-range from 2.6 to 3.1.

Later experiments have confirmed this pH range and even broadened it topH 2.2 to 3.2. Likewise the range of calcium content in mM or mmol/kghas been broadened to:

175-50·pH≦calcium content (mmol/kg)≦660-200·pH.

The pH value is the pH obtained when the solid oral composition isdissolved in an equal amount by weight of highly purified water, i.e.the “effective pH”.

The correlation between effective pH and calcium content in mmol/kg hasbeen illustrated graphically in FIG. 2.

In the following the invention will be further described by examples,which shall not be regarded as limiting for the scope of the invention.

EXAMPLES Example 1 Preparation of Solid Candy

In a mini cooker 800 ml water is added 3 kg isomalt and 0.3 mg sweetener(Acesulfame-K) during stirring. The stirring is continued until ahomogenous solution is obtained. Subsequently the temperature is raisedto about 162° C. and the mixture is boiled. When the temperature hasdecreased to 110° C. the stirring is discontinued and the dough iswithdrawn from the mini cooker and applied on a heated table.

The dough is added 4.5 ml red colour (camine E120) and kneaded so as toobtain a uniform distribution of the colour. Then, 6 ml aroma(strawberry and rhubarb in 2:1 ratio) is added and kneaded into thedough. Subsequently, 30 g tartaric acid (mol weight: 151 g/mol) and 49.5g calcium lactate penta hydrate (mol weight: 308 g/mol) are added andmixed thoroughly with the dough. Long strings of dough are prepared andcut into appropriate pieces of candy. The candy is allowed to cool toroom temperature.

A candy was added an equal amount by weight of water (Millipore®), i.e a1:1 ratio of candy and water was formed, and allowed to stand for 1hour. After an hour the candy was completely dissolved. In the resultingsolution the pH was measured with a calibrated electrode to 2.95.

The mole ratio of calcium component to acid component can then becalculated as

$\frac{49.5\mspace{14mu} g\mspace{14mu} {calcium}\mspace{14mu} {lactate}\mspace{14mu} {penta}\mspace{14mu} {{hydrate}/308}\mspace{14mu} g\text{/}{mole}}{30\mspace{14mu} g\mspace{14mu} {tartaric}\mspace{14mu} {{acid}/151}\mspace{14mu} g\text{/}{mole}} = 0.82$

Example 2 Preparation of Jellies

8 g gelatine (250 Bloom) is dissolved completely in 17 g 80° C. waterunder constant stirring. 4 g dextrose is added to the gelatine solutionunder constant stirring until the mixture is homogenous. Then, 20 gsucrose and 49 g glucose syrup (48 DE) are added and the stirring iscontinued until the mixture is homogeneous. This mixture is then boileduntil brix 75, which happened at 108° C. (vacuum at 0.6 atm). After theboiling step the mixture is added 10 g tartaric acid (mol weight: 151g/mol), 16.5 g calcium lactate penta hydrate (mol weight: 308 g/mol),0.15 ml red colour (camine E120) and 0.6 ml aroma (strawberry andrhubarb in 2:1 ratio) and mixed to obtain a homogenous solution. The pHin the liquid mixture is adjusted with tartaric acid to a pH of 3.2 asmeasured with a standard pH electrode. A sample was withdrawn and mixedwith an equal amount by weight of water. The pH of this diluted samplewas measured as pH 3.2. The mole ratio of calcium component to acidcomponent is

$\frac{{16.5\mspace{14mu} g\mspace{14mu} {calcium}\mspace{14mu} {lactate}\mspace{14mu} {penta}\mspace{14mu} {{hydrate}/308}\mspace{14mu} g\text{/}{mole}}\mspace{14mu}}{10\mspace{14mu} g\mspace{14mu} {tartaric}\mspace{14mu} {{acid}/151}\mspace{14mu} g\text{/}{mole}} = 0.82$

The solution is cast in an adequate shape and allowed to cool to roomtemperature.

Example 3 Test for Erosive Potential of Oral Composition

Candies as produced in example 1 were used in this example to illustratethe erosive potential. A control candy comprising the same components asthe example 1 candy except for calcium lactate was also produced.

Ten randomly selected healthy test persons (5 males and 5 females)sucked 5 grams of the candy habitually for 5 minutes while his/herstimulated whole mouth saliva was collected every 30 seconds for 5minutes. A closed saliva collection system was used to avoid saliva CO₂evaporation and thus pH changes during collection.

Immediately after collection, the pH of the saliva was determined in aclosed system, and the pH was recorded for each of the collections (i.e.first min, second min, etc.). The saliva was then poured into an openglass and salivary CO₂ was removed by vacuum during constant stirringand the sample was acidified (1M HCl) until the pH obtained immediatelyafter collection was reached.

Pure hydroxyapatite crystals (HAp) equal to 2 mg per ml saliva (i.e. 2mM HAp) were added to each of the saliva samples. The grain size of theHAP crystals was 1 μm and they were supplied by Merck Crystals. The pHrise, if any, was recorded continuously at 15-second interval for 5minutes at room temperature. The test procedures mimic an in vivocondition, which is comparable to sucking on 5 gram of the candy for 5minutes in vivo.

In case there was no pH rise, the hard-boiled candy was assessed asnon-erosive.

A pH rise indicated that dissolution of HAp crystals had taken place andthat the candy was erosive. To quantify the amount of dissolved HAp aback titration with acid (1M HCl) was performed 5 minutes after the HAPaddition. The amount of HAp crystals lost per minute in the candycontaining saliva could then be calculated from the amount of μl 1M HClneeded to reach the pH obtained immediately after collection of salivausing the equation stated in example 2.

From the data obtained the erosive potential can be computed as theslope of curve (μg HAp lost per minute of exposure for candy containingsaliva) by linear regression. The result of the experiment is shown onFIG. 1, in which the candy acc. inv. is the candy according to example 1and the control candy is the candy lacking calcium lactate. The resultsshow that the calcium-modified candy according to the invention wasacidic as well as non-erosive due to the interplay between calciumcomponent, saliva buffer capacity, and salivary protein protection.

Example 4

Candies of the compositions indicated in Table 1 were prepared in asimilar manner to Example 1 and tested for erosive potential using thetest method described in example 3 with the results likewise indicatedin the table.

TABLE 1 Ca comp. Ca Acid comp. Acid Ca/acid Effective Test (g) (mmol/kg)(g) (mmol/kg) mole ratio pH Erosive 1 0.0 0 7.0 47 0.00 2.00 YES 2 0.0 05.0 33 0.00 2.25 YES 3 0.0 0 3.0 20 0.00 2.60 YES 4 49.1 160 60.2 4000.40 2.40 NO 5 11.0 36 13.0 87 0.41 2.20 YES 6 16.5 54 18.0 120 0.452.50 NO 7 43.0 140 46.8 311 0.45 2.50 NO 8 10.0 33 10.0 67 0.49 2.40 YES9 16.5 54 16.0 107 0.50 2.64 NO 10 9.0 29 8.0 53 0.55 2.60 YES 11 8.1 267.0 47 0.56 2.70 YES 12 16.5 54 14.0 93 0.57 2.76 NO 13 12.3 40 10.0 670.60 2.87 NO 14 36.8 120 30.1 200 0.60 2.64 NO 15 15.4 50 12.5 83 0.602.84 NO 16 18.5 60 15.0 100 0.60 2.73 NO 17 16.5 54 12.0 80 0.67 2.81 NO18 7.0 23 5.0 33 0.68 2.85 YES 19 27.6 90 22.1 147 0.70 2.81 NO 20 15.049 10.0 67 0.73 2.87 NO 21 16.5 54 10.0 67 0.80 2.91 NO 22 37.0 120 15.0100 1.20 3.24 NO 23 31.0 101 12.5 83 1.21 3.20 NO 24 25.0 81 10.0 671.22 3.27 NO 25 10.7 35 7.3 48 1.25 3.32 NO

Some of the compositions, which were found non-erosive by the test, werefound unsatisfactory from other points of view, either because of theeffective pH being too high to give an adequate saliva stimulatingeffect or because of the calcium content being to high to give anacceptable taste.

The correlation between effective pH and calcium content in mmol/kg fortests 1-25 has been illustrated graphically in FIG. 2, wherein the areabetween the lines Y=660-200·X and Y=175-50·X in the range from X=2.2 to3.2 (marked in grey tone) illustrates compositions according to theinvention (marked with +), i.e. compositions, which have qualified asnon-erosive in human saliva by the above test, have an adequate acidityto provide the desired saliva secretion stimulation, and a calciumcontent, which is sufficiently low to provide an agreeable taste.Compositions marked by ÷ have been found erosive, whereas compositionsmarked by ++ have been found non-erosive, but with an unacceptable tastebecause of an excessive amount of calcium, and the composition marked by+++ non-erosive, but with too low acidity to provide the desired salivasecretion 15 stimulation.

Example 5 Test for Saliva Stimulating Effect

A group of 20 healthy individuals was given a candy of the compositionaccording to test 21, and the amount of saliva produced by sucking thecandy was recorded. The amount of saliva produced by sucking the candywas compared with the amount of saliva produced by the same individualswithin the same period of time without any stimulation of the salivaproduction. The test showed a more than tenfold increase in salivaproduction by sucking the candy.

A corresponding test carried out on a group of 10 dry mouth patientsshowed a fold increase in saliva production by sucking a candy of thecomposition according to test 21.

1. An acidic solid oral composition, which is a boiled sweet, a candy, alollipop, a jelly, a chewing gum, a drop, a pastille, a lozenge, an icecream, a sorbet or a tablet, with reduced erosive potential in saliva,comprising a calcium component and an acid component, wherein theamounts of calcium component and acid component in the solid oralcomposition are adjusted so as to provide (i) a pH in the range of 2.2to 3.2, when the solid oral composition is dissolved in an equal amountby weight of highly purified water, and (ii) a calcium content in theacidic solid oral composition within the following limits:175−(50·pH)≦calcium content (mmol/kg)≦660−(200·pH), the pH being asindicated above, with the proviso that the composition does not includea polyphosphate being a phosphate polymer wherein the number ofphosphate groups (n) is at least
 3. 2. A solid composition according toclaim 1, wherein the mole ratio of calcium component to acid componentis in the range of 0.3 to 0.8.
 3. A solid composition according to claim2, wherein the mole ratio of calcium component to acid component is inthe range of 0.4 to 0.7.
 4. A solid composition according to claim 1,wherein the pH, determined as indicated in claim 1, is between 2.5 and3.2.
 5. A solid composition according to claim 4, wherein the pH,determined as indicated in claim 1, is between 2.6 and 3.1.
 6. A solidcomposition according to claim 1, wherein the calcium component isselected among calcium carbonate, calcium hydroxide, calcium citrate,calcium malate, calcium lactate, calcium chloride, calciumglycerophosphate, calcium acetate, calcium sulphate, and calciumformate, or hydrates or combinations thereof.
 7. A solid compositionaccording to claim 6, wherein the calcium component is calcium lactate.8. A solid composition according to claim 1, wherein the acid componentis selected from the group consisting of citric acid, malic acid,ascorbic acid, tartaric acid, acetic acid, fumaric acid and lactic acid.9. A solid composition according to claim 1, which is intended for beingsucked or chewed.
 10. A method for stimulating the saliva production inan individual comprising orally administering a solid compositionaccording to claim 1 to the individual.
 11. A method according to claim10, which is not for treatment of the human or animal body by therapy.12. A method according to claim 10, for alleviating the sufferings of anindividual having impaired saliva production.
 13. A method according toclaim 12, wherein the impaired saliva production is caused by a diseasesuch as Sjögren's syndrome, cystic fibrosis, diabetes or an eatingdisorder.
 14. A method according to claim 12, wherein the impairedsaliva production is caused by a therapeutic treatment, such as amedical treatment or radiotherapy.
 15. A method for determining theerosive potential in saliva of an oral composition, comprising the stepsof: bringing the oral composition to be tested into contact with salivain the mouth, collecting a sample of the saliva under conditions so asto prevent CO₂ from escaping from the sample, measuring the pH of thesample collected under b), removing CO₂ from the sample, optionallyassisted by vacuum and/or addition of a non-volatile acid, adjusting thepH of the sample to the value measured under c) using a non-volatileacid or, if necessary, a non-volatile base, adding tooth substance tothe sample obtained from step e), and observing any rise in the pH, if arise in pH is observed in step f), titrating the sample to the pH valuemeasured in c) using an acid, and calculating the amount of toothsubstance eroded based on the amount of acid consumed in step g). 16.The method according to claim 15, wherein the non-volatile acidoptionally used in step d) is a strong acid.
 17. The method according toclaim 15, wherein the non-volatile acid is HCl or HNO₃.
 18. The methodaccording to claim 15, wherein the tooth substance is hydroxyapatite.19. The method according to 18, wherein the hydroxyapatite is ofnon-dental origin.
 20. The method according to claim 15, wherein theacid used for titration is HCl.
 21. A solid composition according toclaim 1, which, when tested in randomly selected healthy test persons bya method comprising the steps of: bringing the oral composition to betested into contact with saliva in the mouth, collecting a sample of thesaliva under conditions so as to prevent CO₂ from escaping from thesample, measuring the pH of the sample collected under b), removing CO₂from the sample, optionally assisted by vacuum and/or addition of anon-volatile strong acid, adjusting the pH of the sample to the valuemeasured under c) using a non-volatile acid or, if necessary, anon-volatile base, adding tooth substance to the sample obtained fromstep e), and observing any rise in the pH, if a rise in pH is observedin step f), titrating the sample to the pH value measured in c) using anacid, and calculating the amount of tooth substance eroded based on theamount of acid consumed in step g), no rise in pH in step f) isobserved, within a period of 5 minutes for at least 90% of the testpersons.